Giraffe genes were transferred into mice, but the mice did not grow long necks, but...

Produced by: Science Popularization China

Produced by: Su Chengyu

Producer: Computer Network Information Center, Chinese Academy of Sciences

Giraffes are very conspicuous animals on the savannah. Their long necks have attracted many strange questions. On Zhihu, you can see many myths related to giraffes, such as how do giraffes drink water? Do giraffes have cervical spondylosis? What if a giraffe wants to vomit? Are giraffes easily struck by lightning? What should a giraffe do when it wants to vomit? ...

These strange myths are just because it has the longest neck on earth. The benefits of such a long neck of the giraffe are of course not just to eat leaves high up, but also to get a higher line of sight, a wider field of vision, and to prey on the animals they want more easily than those short-necked animals.

I have given scientific answers to the above questions. If you are interested, you can search and see them. Today we are going to discuss another question about giraffes, a question that is more related to the survival of giraffes: With such a long neck, is it difficult for a giraffe to supply blood from its heart to its head?

Image source: sciencealert

Giraffe with a strong heart

We all know that if you want to pump water from a deep well, in addition to using a rope to tie a bucket down and sink it to scoop up the water, there is another way, which is to use a water pump. Generally speaking, a pump can increase the pressure of the water, and after increasing the pressure, it can obtain greater propulsion force, which can push the water up from underground. The deeper the well, the greater the discharge pressure of the pump required.

The powerful heart of animals is a natural pump that transports blood to all parts of the body through the rhythmic contraction and relaxation of the ventricular muscles. For most mammals, the vertical distance between the heart and the head is short. Therefore, the blood pressure in the heart is similar to that in the head.

But giraffes are different from other "ordinary" mammals. The distance between their heart and head is too long. Therefore, in order to pump blood from the heart to the head, they need a higher arterial blood pressure than other "ordinary" animals to pump the blood up.

As early as 1955, GOETZ RH conducted research on the cardiovascular system of giraffes. He found that the systolic blood pressure of giraffes can reach 300 mmHg and the diastolic blood pressure can reach 180 mmHg, which is about 2.5 times that of normal people. Scientists also found that when a giraffe is not yet fully grown, its head is not that far from the heart, and its blood pressure is relatively low. As the giraffe grows up and its neck becomes longer, its blood pressure also increases.

Comparison of blood pressure in different parts of humans and giraffes Source: Deranged Physiology

Since this natural pump is so powerful, its size must be different from that of an "ordinary" mammal's heart. An adult giraffe's heart is 0.6 meters long and weighs 11 kilograms. Compared to a human heart, which is only about the size of a palm, a giraffe's heart is about 30 times larger than a human's. (I found a picture of a giraffe's heart online, but it's too gory so I won't post it here. If you're interested, you can find it yourself)

But this is not the biggest difference between the hearts of "ordinary" mammals, because the size of the giraffe's heart is proportional to its volume. The biggest difference lies in the internal structure of the heart. From 2006 to 2009, G. Mitchell conducted anatomical observations on giraffes killed every year in Zimbabwe. (Note: Giraffes are killed according to Zimbabwean law).

Scientists have found that the thickness of the left ventricle and ventricular septum of a giraffe is much greater than that of humans. The left ventricle wall of an adult giraffe weighing 1,300 kg can be about 7 cm thick, and the ventricular septum can be about 5 cm thick. It should be noted that the left ventricle wall and ventricular septum of humans are only about 1.2 cm thick, and the ventricular wall thickness of athletes undergoing high-intensity training is slightly higher than that of ordinary people (1.3-1.5 cm).

A cross section of the ventricle of a 1300kg giraffe. Its ventricular wall appears extremely thick.

Source: Document 1

At the same time, scientists have found that the walls of blood vessels in other parts of the giraffe are also very thick, as shown below

Source: Document 1

After analyzing the data, it was found that the thickness of the ventricular wall is an allometric growth relationship. Allometric growth means that the characteristics of an organism will change with the change of body size, but this change is not proportional.

Scientists' discovery of the thickness of giraffe's ventricular wall and arterial wall explains the physiological reason why giraffes do not suffer from high blood pressure. If a person's blood pressure is too high, it means that the pressure pumped out by the heart is too great. This force is too great, and the "thin" blood vessel wall cannot withstand it. The so-called cerebral hemorrhage is caused by the high blood pressure, which bursts the cerebral blood vessel wall.

However, the ventricular walls and blood vessel walls of a giraffe are somewhat different. Its blood vessel walls are extremely thick, several times thicker than those of humans. So even if it has high blood pressure, it does not have to worry about breaking through the blood vessel walls.

But this is not the most fundamental reason. The most fundamental reason lies in genetic differences.

Special gene makes giraffes no longer afraid of high blood pressure

A few years ago, Rasmus Heller launched the Ruminant Genome Project (RGP), which included giraffes. By comparing the genomes of giraffes and other short-necked ruminants, scientists found about 500 genes that are either unique to giraffes or have variations that are only found in giraffes.

Of the 500 genes, one, called FGFRL1, stood out because it was the most different. In humans, this gene appears to be involved in cardiovascular development and bone growth, so the scientists speculated that it might also play a role in giraffes' adaptation to high blood pressure.

To verify their idea, scientists transferred the gene to mice, which are so-called transgenic mice. After 28 days of research, they looked no different from ordinary mice, and these transgenic mice did not grow the iconic long necks of giraffes.

There is no difference from the appearance. Source: Document 2

But there are subtle changes in their bodies...

First, the mice that had been given the giraffe gene had slower bone development in the womb than normal mice. However, once they were born, the transgenic mice grew faster than normal mice. When scientists studied their bones, they found that the transgenic mice had higher bone mineral density.

WT is a normal rat, and giraffe is a rat that has been transferred with the giraffe gene. Obviously, from the CT images, it can be seen that the bone density of the transgenic mice has increased a lot compared to normal rats. Image source: Reference 2

This is a compensatory mechanism that prevents the rapidly growing bone structure from becoming fragile. Scientists speculate that FGFRL1 may be the reason why giraffes grow fast and stably.

Next, the scientists injected angiotensin into the transgenic mice and normal mice.

After being injected with Ang II (a drug that can induce high blood pressure), it was found that the blood pressure of the transgenic mice only rose slightly and their organs were basically unaffected; while the blood pressure of normal mice soared after being injected with the drug, and a large amount of fibrosis (a form of organ damage) appeared in their kidneys and hearts.

Comparison of myocardial fibrosis in transgenic rats and normal rats after angiotensin injection. Myocardial fibrosis in transgenic rats is much lower than that in normal rats. Source: Reference 2

Comparison of renal fibrosis in transgenic rats and normal rats after angiotensin injection. The renal fibrosis in transgenic rats is much lower than that in normal rats. Source: Reference 2

This shows that it is FGFRL1 that gives giraffes unique evolutionary adaptability in dealing with hypertension.

Seeing this, you may wonder if humans can fight high blood pressure by transferring this gene. Of course, not so fast. First, genetically modifying humans is unethical and unsafe. On the other hand, if a gene transfer can cause mutation, and it is a good mutation, then humans would have had Giraffe Man long ago... It's not that simple.

There really is a giraffe man (a villain) in the Marvel Universe. Although he only appeared once and his superpowers have not been made public, I think he should be able to fight high blood pressure...

References:

https://www.sciencedirect.com/science/article/pii/S1095643309010629

https://advances.sciencemag.org/content/7/12/eabe9459

https://pubmed.ncbi.nlm.nih.gov/13274413/

https://www.who.int/features/qa/82/zh/

https://marvel.fandom.com/wiki/Giraffe-Man_(Earth-616)